..In principle, end-point dilution quantitation can be applied to many types of prion and amyloid seeding assays. End point dilution RT-QuIC provides a sensitive, rapid, quantitative, and high throughput assay of prion seeding activity...

Prions and the potential transmissibility of protein misfolding diseases

..This new method enables the relatively rapid and sensitive detection of human CJD and sheep scrapie PrP(res) and may facilitate the development of practical preclinical diagnostic and high-throughput interference tests...

Structure of the flexible amino-terminal domain of prion protein bound to a sulfated glycan

..In contrast, combined expression of anchorless and wild-type PrP produced accelerated clinical scrapie. Thus, the PrP GPI anchor may play a role in the pathogenesis of prion diseases...

Mefloquine, an antimalaria drug with antiprion activity in vitro, lacks activity in vivo

David A KociskoNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USAJ Virol 80:1044-6. 2006

..While most anti-scrapie agent compounds inhibit PrP-res formation in vitro, many PrP-res inhibitors have no activity in vivo. This underscores the importance of testing promising candidates in vivo...

..These results identify new inhibitors of murine and ovine PrP-res formation and reinforce the idea that compounds effective against PrP-res from one species or strain cannot be assumed to be active against others...

..Importantly, there is evidence that combining compounds may provide synergistic responses. This review provides an update on current testing methods, therapeutic targets, and promising candidates for chemical-based therapy...

..Nonetheless, other studies have shown that curcumin is nontoxic and can penetrate the brain, properties that give curcumin advantages over inhibitors previously identified as potential prophylactic and/or therapeutic anti-TSE compounds...

..Both the improved characterization of prion aggregates and the existing atomic models can be used to devise further experiments to better elucidate the misfolding pathway and the structure of prion protofibrils...

Structural insights into the interaction between prion protein and nucleic acid

Abdessamad Tahiri-AlaouiSir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United KingdomJ Biol Chem 281:34171-8. 2006

..It may be that this example of molecular heterosis in vitro provides the basis for maintenance of the polymorphism in the population and that beta-oligomers represent a form of PrP sequestered from pathogenic amyloid formation in vivo...

..On the basis of ultrastructural studies, we suggest that autophagy may play a major role in transmissible spongiform encephalopathies and may even participate in the formation of spongiform change...